We seek to obtain a detailed understanding of the biochemical mechanisms involved in collagen biosynthesis and secretion and the control of these processes. We seek to determine how cells distinguish which proteins are to be secreted, which are to be retained intracellularly, and whether intracellular modification of collagen is necessary for normal secretion. We are studying the factors involved in the normal assembly and stabilization of the collagen triple helix. Through the use of mouse-human hybrid cells, we are studying the genetic control of collagen synthesis and trying to identify the human chromosomes containing the structural genes for the collagen chains as well as modification enzymes. Studies are continuing on the possible translational control of collagen synthesis by specific tRNA species. Collagen is the most prevalent protein in the human body, composing about one-third of total body protein. Because of its widespread distribution and function, collagen is involved either directly or indirectly in many human diseases, both hereditary and acquired. These range from relatively innocuous conditions such as excess scar formation, to the debilitating arthritides, to fatal diseases such as generalized scleroderma. Basic understanding of normal collagen metabolism must precede a rational approach to these diseases.